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. Author manuscript; available in PMC: 2014 Nov 7.
Published in final edited form as: Drug Alcohol Depend. 2012 Jan 9;121(3):189–204. doi: 10.1016/j.drugalcdep.2011.10.031

Figure 10. Longitudinal measures of motivation and compulsivity and relapse in WT and RMOR mice.

Figure 10

A. Lever pressing during the VI period. WT (black) and RMOR mice (gray) expended similar amounts of effort to obtain MS at the start of drinking; however, over time, only WT mice exhibited a progressive increase in responding on the active lever (solid line) (Genotype effect:F[1,82]=16.1,p<0.001 and Genotype x Time interaction: F[2,82]=11.2, p<0.0001). There was no change in responding on the inactive lever (dashed line) in either genotype. B. Latency to earn MS. The latency of WT and RMOR mice to earn morphine was similar at the start of drinking; however, over time, RMOR but not WT mice exhibited a progressive increase in latency (Genotype effect: F[1,82]=13.6, p<0.001 and Genotype x Time interaction: F[2,82]=6.2, p<0.01). C. MS earned during the operant session. The amount of MS earned by WT mice did not change over time despite increased lever pressing. In contrast, RMOR mice showed a progressive decline in MS consumption during the operant session (Genotype effect F[1,82]=57.1, p<0.0001 and Genotype x Time interaction: F[2,82]=8.2, p<0.001). D. Lever pressing during the time-out. WT and RMOR mice initially showed similar amounts of unreinforced lever pressing; however, over time, only WT mice exhibited an increase (Genotype effect: F[1,41]=12.4, p<0.01 and Genotype x Time interaction: F[1,41]=10.6, p<0.01). This effect was restricted to the active lever. E. Suppression of MS seeking by a shock-predictive conditioned stimulus (CS). A CS that had previously been paired with a footshock suppressed MS retrieval to a similar extent in WT and RMOR mice at the start of drinking; however, over time, WT mice became less inhibited compared to RMOR mice (Genotype x Time interaction: F[1,37]=4.3, p<0.05). F. Preference for MS+saccharin versus saccharin alone. RMOR mice initially showed a higher MS preference than WT mice; however, over time, MS preference rose in WT but not RMOR mice (Genotype x Time interaction: F[1,41]=12.5, p<0.01). G. Reinstatement. Reinstatement was induced by the non-contingent delivery of a single MS reinforcer and the contingent presentation of a MS-paired CS. RMOR mice showed significantly less reinstatement than WT mice (p<0.01). (A–F) Data are presented as the mean + SEM. *p<0.05, **p<0.01, ***p<0.001 WT v. RMOR; #p<0.05, ##p<0.01, ###p<0.001 v. earliest time point. Reproduced with permission from Berger, A.C., Whistler, J.L., 2011. Morphine-induced mu opioid receptor trafficking enhances reward yet prevents compulsive drug use. EMBO Mol. Med. 3, 385–397.